OP0048 FIRST INTERIM ANALYSIS OF THE INTERNATIONAL X-LINKED HYPOPHOSPHATAEMIA (XLH) REGISTRY: ADULT POPULATION BASELINE CHARACTERISTICS
Authors: K. Briot, J. Liu, A. Williams, S. Wood
Journal: Annals of the Rheumatic Diseases (2022)

Background X-Linked Hypophosphataemia (XLH) is a rare, progressive, lifelong, hereditary phosphate wasting disorder characterised by a pathological increase in fibroblast growth factor 23 concentration/activity. 1 Despite XLH being increasingly recognised as a chronic progressive disease, there are few data documenting its natural history or the impact of treatment and other medical interventions on patient outcomes. 2 The multicentre, international, XLH patient registry was established to address this lack of information in XLH to help inform future clinical practice. Objectives To report data from the first interim analysis of the International XLH Registry ( NCT03193476 ), focusing on baseline characteristics of adults (aged ≥18 years [y]). Methods The International XLH Registry was initiated August 2017 to collect information on the natural history of XLH and will run for 10 years, aiming to recruit 1,200 people with XLH. Subjects diagnosed with XLH were enrolled from 81 sites in 16 countries (Last Patient In: 30/11/2020; Database Lock: 29/03/2021). Parameters collected at baseline included demographics, medical/treatment history, and clinical presentation. Results In total, 217 adults were eligible for inclusion in this analysis (18–&lt;30y, n=56; 30–&lt;50y, n=96; ≥50y, n=65); and 150 (69.1%) were female. Mean (SD) age was 41.9y (15.5y); median 41.1y. Mean height was 155.8 cm (n=79); mean weight, 70.0 kg (n=96); mean BMI 26.5 kg/m 2 (n=48). Most subjects resided in the UK (50.7%, n=110) and in France (18.9%, n=41). Treatment data were available for 118 subjects: conventional therapy (phosphate salts and active vitamin D), 83.9% (99/118); burosumab, 11.0% (13/118); no treatment recorded 5.1% (6/118). Of 163 subjects with available data, a genetic test result was recorded for 68 (41.7%), of whom 62 (91.2%) had a confirmed PHEX mutation. Data on XLH family history were available for 187 subjects; 56/140 (40.0%) reported their biological mother was affected; and 22/141 (15.6%) reported their biological father was affected. The mean time to diagnosis from first symptoms was longer in older vs younger adults: 18–&lt;30y, 25 months (mo) (n=21); 30–&lt;50y, 21mo (n=21); ≥50y, 112mo (n=13). Retrospective XLH clinical data were available at study entry for 110 adult subjects. Among these subjects, joint conditions were reported by 36.4% (40/110), with osteoarthritis of the knees (60%), hips (42.5%), and shoulders (22.5%) the most frequently affected. Skeletal abnormalities were noted for 71.8% (79/110) of subjects; most common conditions were genu varum 53.2% (42/79), genu valgum 26.6% (21/79), and enthesopathy 21.5% (17/79). Historical fracture data (“yes/no”) were available for 111 subjects; 41 were reported to have had a fracture. Femur fracture was reported for 22 subjects, and hip fractures for 5 subjects. Details of historical orthopaedic surgery were reported for 99 adults; osteotomy was reported for 89 subjects, and hip replacements reported in 14 subjects. Conclusion The demographics and baseline characteristics of subjects in the International XLH Registry are as expected for adults with XLH. The shorter time to diagnosis in younger vs older adults may indicate improved recognition and diagnosis of XLH in recent years. The analysis of this young population treated with conventional therapy highlights the frequency of musculoskeletal involvement (osteoarthritis, enthesopathies, etc). The information collected within this rare-disease registry during these 10 years provides an exciting opportunity to integrate large-scale real-world evidence into clinical practice, with the aim of improving the care and quality of life of people living with this debilitating disease. References [1]Haffner D, et al . Nat Rev Nephrol 2019;15(7):435–455. [2]Padidela R, et al . Orphanet J Rare Dis. 2020; 15:172. Acknowledgements The authors acknowledge the contribution of all members of the International XLH Registry Steering Committee. Disclosure of Interests Karine Briot Speakers bureau: Speakers bureau from KKI, Amgen, UCB, Alexion, Jonathan Liu Employee of: Employed by Kyowa Kirin International, Angela Williams Employee of: Employed by Kyowa Kirin International, Sue Wood Employee of: Employed by Kyowa Kirin International.